To identify points at which RNA metabolism is regulated in whole cells, the rates of processing and wastage of individual methyl-labeled nuclear and cytoplasmic RNA species are being assessed quantitatively in cells in a number of growth states. These include resting cells, human diploid cells at the end of their growth potential, and mutants blocked in processing reactions. The kinetic studies are aided by analysis with a simulation and modeling program (SAAM 23) on an IBM 360 computer. Related studies are being carried out to identify RNases critical for different processes. As a nuclease potentially important for processing reactions, a double-stranded RNase has been isolated from HeLa cell nuclei; and as possible agents in cytoplasmic turnover, RNases of lysosomes are being studied. In projected experiments with various mutants or cells in defined physiological states, correlations between turnover steps and specific enzymes will be sought.